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SH3 & multiple ankyrin repeat domains protein 1; Shank1; somatostatin receptor-interacting protein; SSTR-interacting protein; SSTRIP (SHANK1)
Function:
- seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that interconnects receptors of the postsynaptic membrane including NMDA-receptors & metabotropic glutamate receptors via complexes with GKAP/PSD-95 & homer, respectively, & the actin-based cytoskeleton
- may play a role in the structural & functional organization of the dendritic spine & synaptic junction
- may homomultimerize via its SAM domain (putative)
- interacts with the C-terminus of SSTR2 via the PDZ domain
- interacts with IGSF9, SHARPIN, SPTAN1, HOMER1 & DLGAP1/GKAP isoforms 1 & 2 (putative)
- binds to DAP-1 through its PDZ domain & to homer through one of its proline-rich regions
- part of a complex with DLG4/PSD-95 & DLGAP1/GKAP (putative)
- interacts with BAIAP2
- May also associate with cortactin
- overexpression in cultured neurons leads to enlargement of dendritic spines
Structure:
- belongs to the SHANK family
- contains 6 ANK repeats
- contains 1 PDZ domain (DHR domain)
- contains 1 SAM (sterile alpha motif) domain
- contains 1 SH3 domain
Compartment:
- cytoplasm (putative)
- cell junction, synapse, postsynaptic cell membrane, postsynaptic density
Alternative splicing: named isoforms=3
Expression:
- expressed in brain particularly in the amygdala, hippocampus, substantia nigra & thalamus
- isoform 2 seems to be expressed ubiquitously
Interactions
molecular events
General
ankyrin repeat domain protein (ANKRD)
oligomerizing protein
phosphoprotein
SH3 & multiple anykrin repeat domains (Shank) protein
Properties
SIZE: entity length = 2161 aa
MW = 225 kD
COMPARTMENT: cytoplasm
MOTIF: ankyrin repeat
NAME: ankyrin repeat
SITE: 212-245
ankyrin repeat
NAME: ankyrin repeat
SITE: 246-278
MOTIF: Tyr phosphorylation site {Y275}
ankyrin repeat
NAME: ankyrin repeat
SITE: 279-312
ankyrin repeat
NAME: ankyrin repeat
SITE: 313-345
ankyrin repeat
NAME: ankyrin repeat
SITE: 346-378
ankyrin repeat
NAME: ankyrin repeat
SITE: 379-395
src homology 3 [SH3] domain
SITE: 554-613
PDZ domain
NAME: PDZ domain
SITE: 663-757
histidine-rich region {1002-1007}
MOTIF: histidine residue (SEVERAL)
histidine-rich region {1014-1019}
MOTIF: histidine residue (SEVERAL)
glycine-rich region {1189-1195}
glycine-rich region {1709-1717}
proline-rich region
SITE: 1844-1854
MOTIF: proline residue (SEVERAL)
glycine-rich region {1896-1902}
serine-rich region {1970-1979}
MOTIF: serine residue (SEVERAL)
sterile alpha motif
NAME: sterile alpha motif
SITE: 2098-2161
Database Correlations
OMIM 604999
UniProt Q9Y566
PFAM correlations
Entrez Gene 50944
Kegg hsa:50944
References
- UniProt :accession Q9Y56
- Sheng M.
Molecular organization of the postsynaptic specialization.
Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7058-61. Review.
PMID: 11416187